U.S. patent application number 11/221530 was filed with the patent office on 2006-03-23 for apparatus and method for multi-modal imaging.
Invention is credited to George Brocksieper, Joel N. Helfer, William E. Mclaughlin, Douglas L. Vizard.
Application Number | 20060064000 11/221530 |
Document ID | / |
Family ID | 36074992 |
Filed Date | 2006-03-23 |
United States Patent
Application |
20060064000 |
Kind Code |
A1 |
Vizard; Douglas L. ; et
al. |
March 23, 2006 |
Apparatus and method for multi-modal imaging
Abstract
An imaging system for imaging an object. The imaging system
includes a support member adapted to receive the object in an
immobilized state. The system also includes first means for imaging
the immobilized object in a first imaging mode to capture a first
image, and second means for imaging the immobilized object in a
second imaging mode, different from the first imaging mode, to
capture a second image. The first imaging mode is selected from the
group: x-ray mode and radio isotopic mode. The second imaging mode
is selected from the group: bright-field mode and dark-field mode.
A removable phosphor screen is employed when the first image is
captured and not employed when the second image is captured. The
phosphor screen is adapted to transduce ionizing radiation to
visible light. The phosphor screen is adapted to be removable
without moving the immobilized object. The system can further
include means for generating a third image comprised of the first
and second image.
Inventors: |
Vizard; Douglas L.; (Durham,
CT) ; Helfer; Joel N.; (Cheshire, CT) ;
Brocksieper; George; (Guilford, CT) ; Mclaughlin;
William E.; (Guilford, CT) |
Correspondence
Address: |
Pamela R. Crocker;Eastman Kodak Company
Patent Legal Staff
343 State Street
Rochester
NY
14650-2201
US
|
Family ID: |
36074992 |
Appl. No.: |
11/221530 |
Filed: |
September 8, 2005 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
60611841 |
Sep 21, 2004 |
|
|
|
Current U.S.
Class: |
600/407 |
Current CPC
Class: |
A61B 6/4417 20130101;
A61B 6/508 20130101; A61B 5/0059 20130101; A61B 6/00 20130101; A61B
6/5235 20130101 |
Class at
Publication: |
600/407 |
International
Class: |
A61B 5/05 20060101
A61B005/05 |
Claims
1. An imaging system for imaging a object, comprising: a support
member adapted to receive the object in an immobilized state; a
removable phosphor screen adapted to transduce ionizing radiation
to visible light; first imaging means for imaging the immobilized
object in a first imaging mode to capture a first image; and second
imaging means for imaging the immobilized object in a second
imaging mode, different from the first imaging mode, to capture a
second image, wherein the first and second imaging modes are
selected from the group: bright-field mode, fluorescence mode,
luminescence mode, x-ray mode, and radio isotopic mode.
2. The imaging system of claim 1, further comprising means for
generating a third image comprised of the first and second
image.
3. The imaging system of claim 1, wherein the phosphor screen is
comprised of: a protective layer; a phosphor layer; an optical
layer; and a transparent support layer.
4. The imaging system of claim 3, wherein the protective layer is
reflective.
5. The imaging system of claim 1, wherein the multiple optical
elements enable the location of a common focal plane shared by
differing modes of imaging.
6. An imaging system for imaging an object, comprising: a support
member adapted to receive the object in an immobilized state; first
means for imaging the immobilized object in a first imaging mode to
capture a first image, the first imaging mode being selected from
the group: x-ray imaging mode and isotope imaging mode; second
means for imaging the immobilized object in a second imaging mode
to capture a second image, the second imaging mode being selected
from the group: bright-field imaging mode and dark-field imaging
mode; a phosphor plate disposed proximate the support member when
capturing the first image; and means for removing the phosphor
plate from proximate the support member, without moving the
immobilized object, prior to capture of the second image.
7. The imaging system of claim 6, when the first image is the x-ray
imaging mode, the first means comprises an x-ray source adapted to
transmit x-ray radiation along a path toward the immobilized object
to capture the x-ray image of the immobilized object.
8. The imaging system of claim 6, further comprising means for
generating a third image comprised of the first and second
image.
9. The imaging system of claim 8, further comprising means for
displaying, transmitting, processing, or printing, the third
image.
10. The imaging system of claim 6, wherein the phosphor plate is
comprised of: a protective layer; a phosphor layer; an optical
layer; and a transparent support layer.
11. The imaging system of claim 10, wherein the protective layer is
reflective.
12. The imaging system of claim 6, wherein the multiple optical
elements enable the location of a common focal plane shared by
differing modes of imaging.
13. A method of imaging an object, comprising the steps of:
providing a support member adapted to receive the object in an
immobilized state; providing a phosphor plate adapted to be
disposed proximate the support member when capturing the first
image; with the phosphor plate disposed proximate the support
member, imaging the immobilized object in a first imaging mode to
capture a first image, the first imaging mode being an x-ray mode
and isotope imaging mode; providing means to remove the phosphor
plate from proximate the support member, without moving the
immobilized object; and with the phosphor plate removed from
proximate the support member, imaging the immobilized object in a
second imaging mode to capture a second image, the second imaging
mode being selected from the group: bright-field mode and
dark-field mode.
14. The method of claim 13, further comprising the step of
generating a third image comprised of the first and second
image.
15. The method of claim 14, further comprising the step of
displaying, transmitting, processing, or printing, the third
image.
16. A method of imaging an object, comprising the steps of:
providing a support member adapted to receive the object in an
immobilized state; providing a phosphor plate movable relative to
the support member, without disturbing the immoblized object,
between a first position wherein the phosphor plate is in optical
registration with the support member and a second position wherein
the phosphor plate is not in optical registration with the support
member; capturing an x-ray image or an isotopic image of the
immobilized object when the phosphor plate in disposed in the first
position; and capturing a dark-field image or a bright-field image
of the immobilized object when the phosphor plate in disposed in
the second position.
17. The method of claim 16, further comprising the steps of:
generating a third image comprised of the first and second image;
and displaying, transmitting, processing, or printing, the third
image.
Description
CROSS REFERENCE TO RELATED APPLICATIONS
[0001] Reference is made to commonly assigned Provisional U.S.
Patent Application No. 60/611,841 (Kodak Docket No. 88810/SLP),
entitled "APPARATUS AND METHOD FOR MULTI-MODAL IMAGING", and filed
on Sep. 21, 2004 in the names of Vizard et al., and which is
assigned to the assignee of this application, and incorporated
herein by reference.
FIELD OF THE INVENTION
[0002] The invention relates generally to the field of imaging
systems, and more particularly to the imaging of objects. More
specifically, the invention relates to an apparatus and method
enabling analytical imaging of objects (for example, small animals
and tissue) in differing modes, including bright-field, dark-field
(e.g., luminescence and fluorescence), and x-ray and radioactive
isotopes.
BACKGROUND OF THE INVENTION
[0003] Electronic imaging systems are well known for enabling
molecular imaging. An exemplary electronic imaging system (shown in
FIG. 1 and diagrammatically illustrated in FIG. 2) is the Image
Station 2000MM Multimodal Imaging System 10 available from the
Eastman Kodak Company (refer to www.kodak.com). System 10 includes
a light source 12, an optical compartment 14 which can include a
mirror 16, a lens/camera system 18, and a communication/computer
control system 20 which can include a display device, for example,
a computer monitor. Camera/lens system 18 can include an emission
filter wheel for fluorescent imaging. Light source 12 can include
an excitation filter selector for fluorescent excitation or bright
field color imaging. In operation, an image of an object is
captured using lens/camera system 18. System 18 converts the light
image into an electronic image, which can be digitized. The
digitized image can be displayed on the display device, stored in
memory, transmitted to a remote location, processed to enhance the
image, and/or used to print a permanent copy of the image.
[0004] Applicants have recognized a need for an apparatus and
method for enabling analytical imaging of an object in differing
modes.
SUMMARY OF THE INVENTION
[0005] An object of the present invention is to provide an
apparatus and method for enabling analytical imaging of an
object.
[0006] Another object of the present invention is to provide such
an apparatus and method for enabling analytical imaging of an
object in differing modes.
[0007] These objects are given only by way of illustrative example,
and such objects may be exemplary of one or more embodiments of the
invention. Other desirable objectives and advantages inherently
achieved by the disclosed invention may occur or become apparent to
those skilled in the art. The invention is defined by the appended
claims.
[0008] According to one aspect of the present invention, there is
provided an imaging system for imaging an object. The imaging
system includes a support member adapted to receive the object in
an immobilized state. The system also includes first means for
imaging the immobilized object in a first imaging mode to capture a
first image, and second means for imaging the immobilized object in
a second imaging mode, different from the first imaging mode, to
capture a second image. The first imaging mode is selected from the
group: x-ray mode and radio isotopic mode. The second imaging mode
is selected from the group: bright-field mode and dark-field mode.
A removable phosphor screen is employed when the first image is
captured and not employed when the second image is captured. The
phosphor screen is adapted to transduce ionizing radiation to
visible light. The phosphor screen is adapted to be removable
without moving the immobilized object. The system can further
include means for generating a third image comprised of the first
and second image.
BRIEF DESCRIPTION OF THE DRAWINGS
[0009] The foregoing and other objects, features, and advantages of
the invention will be apparent from the following more particular
description of the embodiments of the invention, as illustrated in
the accompanying drawings. The elements of the drawings are not
necessarily to scale relative to each other.
[0010] FIG. 1 shows a perspective view of an exemplary prior art
electronic imaging system.
[0011] FIG. 2 shows a diagrammatic view of the prior art electronic
imaging system of FIG. 1.
[0012] FIG. 3A shows a diagrammatic side view of the imaging system
in accordance with the present invention.
[0013] FIG. 3B shows a diagrammatic front view of the imaging
system of FIG. 3A.
[0014] FIG. 4 shows a perspective view of the imaging system of
FIGS. 3A and 3B.
[0015] FIG. 5A shows a diagrammatic side view of the sample object
stage.
[0016] FIG. 5B shows a diagrammatic side view of the sample object
stage in the first imaging position P1 wherein the phosphor plate
is disposed proximate the sample object stage.
[0017] FIG. 5C shows a diagrammatic side view of the sample object
stage in the second imaging position P2 wherein the phosphor plate
is not proximate the sample object stage.
[0018] FIG. 6 shows a diagrammatic side view of a section taken
along line 6-6 of FIG. 5B.
[0019] FIG. 7 shows a diagrammatic side view of a section taken
along line 7-7 of FIG. 5C.
[0020] FIG. 8 shows a work flow diagram in accordance with a method
of the present invention.
[0021] FIG. 9A shows a first image of an immobilized object in a
first imaging mode.
[0022] FIG. 9B shows a second image of the immobilized object of
FIG. 9A in a second imaging mode.
[0023] FIG. 9C shows an image generated by the merger of the images
of FIGS. 9A and 9B.
[0024] FIG. 10A shows a first image of an immobilized object in a
first imaging mode.
[0025] FIG. 10B shows a second image of the immobilized object of
FIG. 10A in a second imaging mode.
[0026] FIG. 10C shows an image generated by the merger of the
images of FIGS. 10A and 10B.
[0027] FIG. 11A shows a first image of an immobilized object in a
first imaging mode.
[0028] FIG. 11B shows a second image of the immobilized object of
FIG. 11A in a second imaging mode.
[0029] FIG. 11C shows an image generated by the merger of the
images of FIGS. 11A and 11B.
[0030] FIG. 12 is a diagrammatic view of a suitable phosphor plate
for use with the apparatus and method of the present invention.
[0031] FIG. 13 is a flow diagram of a method for making a phosphor
plate of FIG. 12.
DETAILED DESCRIPTION OF THE INVENTION
[0032] The following is a detailed description of the preferred
embodiments of the invention, reference being made to the drawings
in which the same reference numerals identify the same elements of
structure in each of the several figures.
[0033] Applicants have recognized that the complex pharmaceutical
analyses of small objects/subjects (e.g., small animal and tissue)
images are particularly enhanced by using different in-vivo imaging
modalities. Using the known/current practices of bright-field,
dark-field and radiographic imaging for the analysis of small
objects/subjects (such as a mouse) can be expensive and may not
provide the precision of co-registered images that is desired.
[0034] Using the apparatus and method of the present invention,
precisely co-registered fluorescent, luminescent and/or isotopic
probes within an object (e.g., a live animal and tissue) can be
localized and multiple images can be accurately overlaid onto the
simple bright-field reflected image or anatomical x-ray of the same
animal within minutes of animal immobilization.
[0035] The present invention uses the same imaging system to
capture differing modes of imaging, thereby enabling/simplifying
multi-modal imaging. In addition, the relative movement of probes
can be kinetically resolved over the time period that the animal is
effectively immobilized (which can be tens of minutes).
Alternatively, the same animal may be subject to repeated complete
image analysis over a period of days/weeks required to assure
completion of a pharmaceutical study, with the assurance that the
precise anatomical frame of reference (particularly, the x-ray) may
be readily reproduced upon repositioning the object animal. The
method of the present invention can be applied to other objects
and/or complex systems subject to simple planar imaging
methodologies.
[0036] More particularly, using the imaging system of the present
invention, an immobilized object can be imaged in several imaging
modes without changing/moving the immobilized object. These
acquired multi-modal images can then be merged to provide a
co-registered image for analysis.
[0037] Imaging modes supported by the apparatus/method of the
present invention include: x-ray imaging, bright-field imaging,
dark-field imaging (including luminescence imaging, fluorescence
imaging) and radioactive isotope imaging. Images acquired in these
modes can be merged in various combinations for analysis. For
example, an x-ray image of the object can be merged with a near IR
fluorescence image of the object to provide a new image for
analysis.
[0038] The apparatus of the present invention is now described with
reference to FIGS. 3A, 3B, and 4 wherein FIG. 3A shows a
diagrammatic side view of an imaging system 100 in accordance with
the present invention, FIG. 3B shows a diagrammatic front view of
imaging system 100, and FIG. 4 shows a perspective view of imaging
system 100.
[0039] Imaging system 100 includes light source 12, optical
compartment 14, a lens/camera system 18, and communication/computer
control system 20 which can include a display device, for example,
a computer monitor. Camera/lens system 18 can include an emission
filter wheel for fluorescent imaging. Light source 12 can include
an excitation filter selector for fluorescent excitation or bright
field color imaging.
[0040] As best shown in FIG. 3A, imaging system 100 includes an
x-ray source 102 and a sample object stage 104. Imaging system 100
further comprises epi-illumination, for example, using fiber optics
106, which directs conditioned light (of appropriate wavelength and
divergence) toward sample object stage 104 to provide bright-field
or fluorescent imaging.
[0041] Sample object stage 104 is disposed within a sample
environment 108, which allows access to the object being imaged.
Preferably, sample environment 108 is light-tight and fitted with
light-locked gas ports for environmental control. Such
environmental control might be desirable for controlled x-ray
imaging or for support of particular specimens.
[0042] Imaging system 100 can include an access means/member 110 to
provide convenient, safe and light-tight access to sample
environment 108. Access means are well known to those skilled in
the art and can include a door, opening, labyrinth, and the like.
Additionally, sample environment 108 is preferably adapted to
provide atmospheric control for sample maintenance or soft x-ray
transmission (e.g., temperature/humidity/alternative gases and the
like).
[0043] Sample object stage 104 is disposed within a sample
environment 108, which allows is access to the object being imaged.
Preferably, sample environment 108 is light-tight and fitted with
light-locked gas ports for environmental control. Environmental
control enables practical x-ray contrast below 8 Kev (air
absorption) and aids in life support for biological specimens.
[0044] Accordingly, imaging system 100 further includes an access
means/member 110 to provide convenient, safe and light-tight access
to sample environment 19. Access means are well known to those
skilled in the art and can include a door, opening, labyrinth, and
the like. Additionally, sample environment 108 is preferably
adapted to provide atmospheric control for sample maintenance or
soft x-ray transmission (e.g., temperature/humidity/alterative
gases and the like).
[0045] Imaging system 100 can be a unitary system. Alternatively,
imaging system 100 can be a modular unit adapted to be used/mated
with electronic imaging system such as electronic imaging system
10.
[0046] FIGS. 5-7 more particularly illustrate elements of sample
object stage 104 and an optical interface relative with the focal
plane of camera/lens system 18.
[0047] FIG. 5A shows a diagrammatic side view of sample object
stage 104 showing the relative movement of the phosphor plate
relative to the sample object stage. FIG. 5B shows a diagrammatic
side view of the sample object stage in a first imaging position P1
wherein the phosphor plate is disposed proximate the sample object
stage. FIG. 5C shows a diagrammatic side view of the sample object
stage in the second imaging position P2 wherein the phosphor plate
is not proximate the sample object stage.
[0048] FIG. 6 shows a diagrammatic side view of a section taken
along line 6-6 of FIG. 5B, which corresponds with the first imaging
position P1. FIG. 7 shows a diagrammatic side view of a section
taken along line 7-7 of FIG. 5C, which corresponds with the second
imaging position P2.
[0049] Sample object stage 104 includes a frame 120 to support and
stretch a thin plastic support sheet 122. Support sheet 122 is
selected so as to support a sample weight (i.e., the weight of a
sample) and is optically clear and free of significant interfering
fluorescence.
[0050] A phosphor plate 125 is mounted for motion toward and away
from sample object stage 104. While those skilled in the art might
recognize other configurations, in a preferred embodiment, phosphor
plate 125 is mounted for translation to provide slidable motion (in
the direction of arrow A) relative to frame 120, beneath the
sample, in intimate contact with support sheet 122. As will be more
particularly described below, in a first imaging position P1,
phosphor plate 125 is in overlapping arrangement with sample object
stage 104 (FIG. 6) when an x-ray image of the object is captured. A
second imaging position P2 is defined when phosphor plate 125 is
translated/moved away from sample object stage 104 (FIG. 7) for
capture of an image of the object such that phosphor plate 125 is
not imaged when an image of the object is captured in second
imaging position P2.
[0051] Frame 100 and phosphor plate 125 are mounted for slidable
motion relative to each other. Such motion can be accomplished
using methods known to those skilled in the art, for example, frame
100 and phosphor plate 125 can be disposed on rails supported by a
surface of an optical platen 126.
[0052] FIG. 6 provides an expanded view of sample object stage 104
including phosphor plate 125 to more particularly show a focal
plane (quoting relevant thickness).
[0053] Sample support sheet 122 is preferably comprised of Mylar or
polycarbonate and has a nominal thickness of about 0.1 mm.
[0054] A protective layer 128 (for example, reflective Mylar) of
about 0.025 mm is provided to protect the phosphor surface of
phosphor plate 125. Protective layer 128 promotes/increases the
image-forming light output. In a preferred embodiment, protective
layer 128 is reflective so as to prevent object reflection back
into the image-forming screen, reducing the confusing the ionizing
radiation image.
[0055] A phosphor layer 130 is provided to transduce ionizing
radiation to visible light practically managed by a lens and a
camera (such as a CCD camera). Phosphor layer 130 can have a
thickness ranging from about 0.01 mm to about 0.1 mm, depending
upon the application (i.e., soft x-ray, gamma-ray or fast electron
imaging).
[0056] An optical layer 132 is provided for conditioning emitted
light from phosphor layer 130. Optical layer 132 can have a
thickness in the range of less than about 0.001 mm.
[0057] Particular information about phosphor layer 130 and optical
layer 132 are disclosed in U.S. Pat. No. 6,444,988 (Vizard),
commonly assigned and incorporated herein by reference.
[0058] A supporting glass plate 134 is provided. Glass plate 134 is
spaced at a suitable mechanical clearance from an optical platen
126, for example, by an air gap/void 136. In the preferred
embodiment, the surfaces of clear optical media (e.g., a lower
surface of glass plate 134 and both surfaces of optical platen 126)
are subject to anti-reflective coating to minimize reflections that
may confuse the image of the object.
[0059] FIG. 7 provides an expanded view of sample object stage 13
including wherein phosphor plate 125 is removed (i.e., taken along
line 7-7 of FIG. 5C). As shown in FIG. 7 is frame 120, sample
support sheet 122, an air gap/void 138 (since phosphor plate 125 is
removed), and optical platen 126.
[0060] Referring now to FIG. 8, in operation, an object (such as a
small animal) is immobilized on sample object stage 104 (step 200).
An operator configures system 100 for imaging in a first mode, and
an image of the object is captured using lens/camera system 18 in
the first mode (step 202). System 18 converts the light image into
an electronic image which can be digitized. This digitized image is
referred to as Image1 or I1. The digitized image can be displayed
on the display device, stored in memory, transmitted to a remote
location, processed to enhance the image, and/or used to print a
permanent copy of the image. The object remains immobilized on
sample object stage 104; no change in the position/location of the
object is made. The operator configures system 100 for imaging in a
second mode (step 204), and an image of the object is captured
using lens/camera system 18 in the second mode. The resulting
digitized image is referred to as Image2 or I2. Since the position
of the object was not moved/changed during the capture of the
images, both Image1 and Image2 can readily be merged or
superimposed, using methods known to those skilled in the art, such
that the two images are co-registered. As such, a third image can
be generated comprising Image1 and Image2.
[0061] As indicated above, system 100 can be configured in several
modes, including: x-ray imaging, bright-field imaging, dark-field
imaging (including luminescence imaging, fluorescence imaging) and
radioactive isotope imaging.
[0062] To configure system 100 for x-ray imaging or isotope
imaging, phosphor plate 125 is positioned in optical registration
with sample object stage 104 (as shown in FIGS. 5B and 6). For an
x-ray image, x-ray source 102 is employed when capturing the image
of the immobilized object.
[0063] To configure system 100 for bright-field imaging or
dark-field imaging (including luminescence imaging and fluorescence
imaging), phosphor plate 125 is removed from optical registration
with sample object stage 104 (as shown in FIGS. 5C and 7), and an
image of the immobilized object is appropriately captured.
[0064] The object is immobilized on sample object stage 104, and
light emitted from the object (usually diffusive within the turbid
constituents of a solid object) is projected to the object surface,
which intimately bears upon the upper surface of sample support
sheet 122.
[0065] For the purpose of optical imaging, the object surface is
defined by a refractive boundary (e.g., the skin of an animal) that
delineates the interior of the object (usually a heterogeneous,
turbid media of higher index of refraction) and air. Light
emanating from within an object (e.g., luminescent or transmitted)
projects to the surface from which it scatters, defining the light
that may be productively managed to create an image of the object.
Conversely, light may be provided from beneath optical platen 126
and scattered from the object surface, thereby providing reflective
light for imaging the same object.
[0066] For optical imaging, the definition of the object boundary
may be moderated by matching the refractive index of the object
boundary to support sheet 122 by introducing an index-matching
fluid (e.g., water). The depth to which good focus can be achieved
in optical imaging is dependent on minimizing the surface scatter
of the object, and methods such as index matching and increasing
wavelength (e.g., near-infrared, NIR imaging) are is well known in
the art.
[0067] The depth to which good focus can be achieved in optical
imaging is dependent on minimizing the surface scatter of the
object, and methods such as index matching and increasing
wavelength (e.g., near-infrared, NIR imaging) are well known in the
art.
[0068] The emitted sample light can arise from luminescence,
fluorescent or reflection, and the focal plane of the lens can be
adjusted to the elevation of object surface. Alternatively, the
"light" can be ionizing radiation passing through or emitted from
the object, or passing into the phosphor and forming an image. Soft
x-rays, consistent with thin objects or small animals, project an
image through the diffusive phosphor onto the optical boundary,
adding the depth of the (more than about 0.02 mm) to the depth of
focus. More significant is the focal distance contributed by the
phosphor support plate 134, which may be fractional millimeters,
depending upon the thickness and index of the glass or plastic. The
fractional-millimeter elevation of the best focal plane contributed
by the phosphor support can provide a better coincidence between
the phosphor focal plane and the focal plane used for optical
imaging. For NIR optical imaging, the preferred/best focal plane
may be located at millimeter depths into a nominally turbid object.
The phosphor support plate 134 can be thicker to maximize the
coincidence of the optical and phosphor imaging planes. Those
skilled in the art will recognize how to tune the materials of the
present invention to optimally co-locate the preferred optical and
phosphor imaging planes. Currently described materials may be
practically assembled to assure multi-modal focal plane co-location
to accommodate the demands of a fast lens system.
[0069] Appropriately fast lens systems for dark-field and x-ray
imaging applications will likely have sub-millimeter focal depths,
necessitating the above considerations. Accordingly, for a
particular embodiment, it may be desirable for multiple optical
elements to enable the location of a common focal plane shared by
differing modes of imaging.
[0070] Emitted gamma rays from a thick object (such as 99Tc
emission from an animal organ) is distributed over the plane of the
phosphor, diffusing the image by millimeters, and an appropriately
thick phosphor screen (about 0.1 mm) may be preferred for increased
detection efficiency. Consequently, the location of the focal plane
at the supporting sheet is not critical to the resolution of the
radio isotopic image. Better resolution and more precise planar
projection of the emitting isotope can be achieved by gamma-ray
collimation. Collimators of millimeter-resolution are available and
capable of projecting isotopic location to millimeter resolution at
the focal plane of the phosphor in the present invention.
[0071] Of particular relevance to the operation of the present
invention is the thickness of the layers in the focal plane of the
lens. For example, fast lenses, (which are essential elements for
the practice of imaging low-light emissions) will have a focal
depth of focus of about 0.5 mm for very fast lenses. For good
resolution of objects of interest, less than about 0.2 mm of
spatial resolution is desirable, and a megapixel CCD camera
(cooled) imaging at 100 mm field is suitable. Generally, more
resolution is desirable.
[0072] Precision registration of the multi-modal image can be
accomplished using methods known to those skilled in the art. By
placing the object on a thin, stretched optical support that allows
phosphor plate 125 to be removed without displacement of the
object, co-registered optical imaging is enabled by the same
lens/camera system using epi-illumination methodologies at a
sufficiently similar focal plane.
[0073] Examples are now provided.
[0074] Referring to FIGS. 9A-9C, there is shown images captured
using the apparatus and method of the present invention. A mouse
was immobilized on sample object stage 104 (step 200 of FIG. 8) of
system 100. System 100 was first configured for near IR
fluorescence imaging wherein phosphor plate 125 is removed from
co-registration with frame 100. A first image was captured and is
displayed in FIG. 9A (step 202 of FIG. 8). Next, system 100 was
configured for x-ray imaging wherein phosphor plate 125 is placed
in co-registration with frame 100. A second image was captured and
is displayed in FIG. 9B (step 204 of FIG. 8). Using methods known
to those skilled in the art, the first and second images were
merged (step 206 of FIG. 8) and the merged image is displayed in
FIG. 9C. Note that the fluorescent signals superimposed on the
anatomical reference clarify the assignment of signal to the
bladder and an expected tumor in the neck area of this illustrated
experimental mouse.
[0075] It is noted that the first and/or second image can be
enhanced using known image processing methods/means prior to be
merged together. Alternatively, the merged image can be enhanced
using known image processing methods/means. Often, false color is
used to distinguish fluorescent signal from gray-scale x-rays in a
merged image.
[0076] FIGS. 10A-10C provide a further example using the apparatus
and method of the present invention. FIG. 10A is a near IR
fluorescence image of a mouse while FIG. 10B is an x-ray image of
the same immobilized mouse. Using methods known to those skilled in
the art, the first and second images were merged and the merged
image is displayed in FIG. 10C. Prior to being merged, the first
and second images were contrasted. This processing allows
particular areas of the mouse to be visually enhanced for
diagnostic purposes. For example, areas 150,152, and 156 are
potential secondary early detection sites, and area 154 shows the
primary tumor injection site at the knee.
[0077] FIGS. 11A-11C provide yet a further example using the
apparatus and method of the present invention. FIG. 11A is a near
IR fluorescence image of a mouse wrist while FIG. 11B is an x-ray
image of the same immobilized mouse wrist. Using methods known to
those skilled in the art, the first and second images were merged
and the merged image is displayed in FIG. 11C. The merged image
provides a diagnostic image for viewing a potential secondary tumor
site. Note that this image set clearly demonstrates the precision
to which the current invention enables the co-location of objects
from differing imaging modes. The maximum fluorescent signal
emanating from a pre-metastatic tumor on the radius (arm-bone) tip
at the wrist is within about 0.1 mm of the suspect lesion
subsequently identified by microscopic histology.
[0078] A phosphor plate suitable for use with the apparatus and
method of the present invention is disclosed in U.S. Pat. No.
6,444,988 (Vizard), commonly assigned and incorporated herein by
reference. A description of the phosphor plate described in Vizard
is now provided.
[0079] Referring now to FIG. 12, there is shown a suitable phosphor
plate 125A for use with the apparatus and method of the present
invention. As shown, plate 125A includes a transparent support 210
(such as glass) upon which is coated an interference filter 220
which is a multicoated short-pass filter designed to transmit light
at a specified wavelength (and below) and reflect light above that
wavelength. Plate 125A also includes a thin phosphor layer 240 and
a removable thick phosphor layer 260. Thin phosphor layer 240 is
used for high resolution imaging applications of ionizing radiation
or for very low energy (self-attenuating) ionizing radiation such
as low-energy electrons or beta particles. Thick phosphor layer 260
is used for high energy ionizing radiation that freely penetrates
the phosphor. Thick phosphor layer 260 is removable and is shown in
FIG. 12 overlaying thin phosphor layer 240. Layer 260 is removable
to the position shown in dashed lines out of contact with layer
240.
[0080] The phosphor preferably used in phosphor layers 240 and 260
is Gadolinium Oxysulfide: Terbium whose strong monochromatic line
output (544-548 nanometers (NM) is ideal for co-application with
interference optics. This phosphor has technical superiority
regarding linear dynamic range of output, sufficiently "live" or
prompt emission and time reciprocity, and intrascenic dynamic range
which exceed other phosphors and capture media. This phosphor layer
preferably has a nominal thickness of 10-30 micrometers (.mu.m) at
5-20 grams/square foot (g/ft2) of phosphor coverage, optimally
absorbing 10-30 Kev x-rays. Thick phosphor layer 260 has a nominal
thickness of 100 .mu.m at 80 g/ft2 of phosphor coverage.
[0081] The duplex phosphor layers impart flexibility of usage for
which the thick phosphor layer 260 may be removed to enhance the
spatial resolution of the image. Thin phosphor layer 240 intimately
contacts filter 220, whereas thick phosphor layer 260 may be
alternatively placed on thin phosphor layer 240.
[0082] Interference filter 220 transmits light at 551 NM and below
and reflects light above that wavelength. Filter 220 comprises
layers of Zinc Sulfide-Cryolite that exhibits a large reduction in
cutoff wavelength with increasing angle of incidence. The filter
has a high transmission at 540-551 NM to assure good transmission
of 540-548 NM transmission of the GOS phosphor. The filter also has
a sharp short-pass cut-off at about 553 NM, that blue shifts at
about 0.6 NM per angular degree of incidence to optimize optical
gain.
[0083] Glass support 210 should be reasonably flat, clear, and free
of severe defects. The thickness of support 210 can be 2
millimeters. The opposite side 280 of glass support 210 is coated
with an anti-reflective layer (such as Magnesium Fluoride, green
optimized) to increase transmittance and reduce optical artifacts
to ensure that the large dynamic range of the phosphor emittance is
captured.
[0084] Referring now to FIG. 13, there is shown a method of
producing phosphor layer 240. A mixture of GOS:Tb in a binder is
coated on a polytetrafluoroethylene (PTFE) support (box 300). The
PTFE support enables release of the coated phosphor layer from the
PTFE support and subsequent use of the phosphor layer without
support, since conventional supporting materials are an optical
burden to screen performance. For the thin phosphor layer 240, an
ultra thin (about 0.5 g/ft2, 0.5 .mu.m thick) layer of cellulose
acetate overcoat can be applied (box 320) to offer improved
handling characteristics of the thin phosphor layer and to provide
greater environmental protection to the underlying optical
filter.
[0085] The phosphor layer is removed from the PFTE support (box
340). The thin phosphor layer overcoated side is overlayed on
interference filter 220 (box 360). Clean assembly of the thin
phosphor layer 240 and filter 220 assures an optical boundary that
optimizes management of screen light output into the camera of the
lens/camera system. Optical coupling of layer 240 and filter 220 is
not necessary, since performance reduction may result.
[0086] Layer 240 can be sealed around its periphery and around the
periphery of filter 220 for mechanical stability and further
protection of the critical optical boundary against environmental
(e.g., moisture) intrusion (box 380).
[0087] Advantages of the present invention include: provides
anatomical localization of molecular imaging agent signals in small
animals, organs, and tissues; provides precise co-registration of
anatomical x-ray images with optical molecular and radio isotopic
images using one system; promotes improved understanding of imaging
agent's biodistribution through combined use of time lapse
molecular imaging with x-ray imaging; and allows simple switching
between multi-wavelength fluorescence, luminescence,
radio-isotopic, and x-ray imaging modalities without moving the
object/sample.
[0088] The invention has been described in detail with particular
reference to a presently preferred embodiment, but it will be
understood that variations and modifications can be effected within
the spirit and scope of the invention. The presently disclosed
embodiments are therefore considered in all respects to be
illustrative and not restrictive. The scope of the invention is
indicated by the appended claims, and all changes that come within
the meaning and range of equivalents thereof are intended to be
embraced therein.
PARTS LIST
[0089] 10 electronic imaging system [0090] 12 light source [0091]
14 optical compartment [0092] 16 mirror [0093] 18 lens/camera
system [0094] 20 communication/computer control system [0095] 100
imaging system of the present invention [0096] 102 x-ray source
[0097] 104 sample object stage [0098] 106 epi-illumination; fiber
optics [0099] 108 sample environment [0100] 110 access means/member
[0101] 120 frame [0102] 122 support sheet [0103] 125 phosphor plate
[0104] 126 optical platen [0105] 128 protective layer [0106] 130
phosphor layer [0107] 132 optical layer [0108] 134 support plate;
glass [0109] 136 air gap/void [0110] 138 air gap/void
* * * * *
References